Perazil,Burroughs-Wellcome,US,1949
0.08 mol (19 9) of 4-chlorobenzhydryl chloride and 0.16 mol (16 g) of
methylpiperazine were mixed in about 20 cc of dry benzene. The flask
containing the reaction mixture was covered by a watch glass and set in a
steam bath, and heating was continued for 6 hours. The contents of the flask
were partitioned between ether and water and the ethereal layer was washed
with water until the washings were neutral. The ethereal layer was extracted
successively with 30 and 10 cc portions of 3 N hydrochloric acid. On
evaporation of the ether layer there remained a residue of 2.5 9. The aqueous
extracts were united and basified with concentrated alkali. The oily base was
taken into ether and dried over potassium carbonate. On evaporation of the
ether, N-methyl-N'-(4-chlorobenzhydryl) piperazine was recovered in the form
of a viscous oil in 75% yield. The N-methyl-N'-(4-chlorobenzhydryl) piperazine
was dissolved in absolute alcohol and ethanolic hydrogen chloride added in
excess. The dihydrochloride crystallized on addition of absolute ether and was
recrystallized from the same solvent mixture in the form of longish prisms
melting at about 216°C.
Chlorcyclizinehydrochloride, 1-(p-chloro-α-phenylbenzyl)-4-methylpiperazinemonohydrochioride, is a light-sensitive, white crystallinepowder that is soluble in water (1:2), in alcohol(1:11), and in chloroform (1:4). A 1% solution has a pH between4.8 and 5.5. Disubstitution or substitution of halogenin the 2- or 3-position of the benzhydryl rings results in amuch less potent compound. Chlorcydizine is indicated forthe symptomatic relief of urticaria, hay fever, and certainother conditions.
